Pseudomonas aeruginosa Bacteremia in Patients Infected with Human Immunodeficiency Virus Type 1

 A prospective analysis of 43 episodes of Pseudomonas aeruginosa bacteremia in HIV-1-infected subjects was performed and the results compared with the incidence and outcome of Pseudomonas aeruginosa bacteremia in other high-risk patients, such as transplant recipients, leukemia patients, or patients hospitalized in the intensive care unit. The incidence of bacteremia/fungemia as a whole and of gram-negative and Pseudomonas aeruginosa bacteremia in particular was greater in HIV-1-infected subjects than in the unselected general population admitted. In contrast, the incidence of Pseudomonas aeruginosa bacteremia in HIV-1-infected patients did not differ from that in patients with other high-risk conditions. In patients with HIV-1 infection, independent risk factors for presenting Pseudomonas aeruginosa bacteremia were nosocomial origin (OR, 2.7; 95% CI, 1.3–5.7), neutropenia (OR, 2.7; 95% CI, 1.07–6.8), previous treatment with cephalosporins (OR, 3.6; 95% CI, 1.1–11.6), and a CD4+ cell count lower than 50 cells/mm³ (OR, 3.1; 95% CI, 1.7–8.6). Primary bacteremia and pneumonia were the most common forms of presentation. Fourteen (33%) patients died as a consequence of the bacteremia. The presence of severe sepsis (OR, 17.5; 95% CI, 3.2–68) and the institution of inappropriate definitive antibiotic therapy (OR, 2.7; 95% CI, 1.1–13) were independently associated with a poor outcome. One year after the development of bacteremia, only eight (19%) patients remained alive.     

Mycobacterium kansasii Infection in Patients Infected with the Human Immunodeficiency Virus

 To investigate the clinical and radiographic features and the response to therapy of Mycobacterium kansasii infection in human immunodeficiency virus-infected patients, the clinical charts of 19 cases diagnosed during a 15-year period were reviewed retrospectively. Most patients were male intravenous drug abusers. Mycobacterium kansasii infection occurred late in the course of HIV disease and was associated with advanced immunosuppression. Thirteen patients had pulmonary disease, three extrapulmonary disease (2 with pulmonary involvement), and three pulmonary colonization. Most of them had fever and nonspecific respiratory symptoms; interstitial and alveolar infiltrates were the most common radiographic findings. Fourteen patients were given antituberculous treatment; among these, a clinical response was observed in 85%. Overall mortality was 63%, but only four patients died from active Mycobacterium kansasii disease. HIV infection has become the most important risk factor for Mycobacterium kansasii disease in our setting. Pulmonary infection is the most frequent form of disease and is usually responsive to antituberculous therapy.     

Hepatitis B Virus DNA in Sera of Blood Donors and of Patients Infected with Hepatitis C Virus and Human Immunodeficiency Virus

With the use of PCR, we searched for hepatitis B virus (HBV) DNA in serum samples from 415 HBsAg-negative, anti-HBc-positive patients: 150 were blood donors, 106 had only hepatitis C virus (HCV) infection, and 159 had human immunodeficiency virus (HIV) infection (of which 88 were HCV positive and 71 were HCV negative). HBV DNA was detected in 4% of blood donors, 3.4% of HIV- and HCV-positive patients, and 24% of HCV-positive patients.     

High Prevalence of GB Virus C/Hepatitis G Virus RNA and Antibodies in Patients Infected with Human Immunodeficiency Virus Type 1

 The prevalence of GB virus C (GBV-C)/ hepatitis G virus (HGV) RNA and antibodies to the structural E2 protein was investigated in a cohort of HIV-1 infected patients. Of 346 individuals, RNA was detected in 143 and E2 antibodies were detected in 73, for an overall prevalence of 62.4%. Intravenous drug use and homosexuality were identified as major transmission risk factors. GBV-C/HGV RNA prevalence was associated with hepatitis B coinfection, whereas antibodies to E2 were associated with older age and lower CD4+ cell counts. GBV-C/HGV infection was frequent in this group of HIV-infected patients and was associated with older age, lower CD4+ cell counts, and the presence of hepatitis B surface antigen.     

Impaired Macrophage Phagocytosis of Apoptotic Neutrophils in Patients with Human Immunodeficiency Virus Type 1 Infection

Dysfunction of neutrophils (polymorphonuclear leukocytes [PMNL]) and macrophagic cells occurs as a consequence of human immunodeficiency virus type 1 (HIV-1) infection. Macrophages contribute to the resolution of early inflammation ingesting PMNL apoptotic bodies. This study investigated macrophage ability to phagocytose PMNL apoptotic bodies in patients with HIV-1 infection in comparison with uninfected individuals and the effect of HIV Nef protein on apoptotic body phagocytosis to determine if phagocytic activity is impaired by HIV infection. Monocytes/macrophages were isolated from 10 HIV-1-infected patients and from five healthy volunteers, whereas PMNL were isolated from healthy volunteers. Macrophage phagocytosis of apoptotic PMNL was determined by staining of apoptotic bodies with fluorescein-conjugated concanavalin A or with fluorescein-labeled phalloidin. Our data show significant impairment of PMNL apoptotic body macrophage phagocytosis in subjects with HIV-1 infection presenting a concentration of CD4⁺ T lymphocytes of >200/mm³ and in particular in those with <200 CD4⁺ T lymphocyte cells/mm³. In addition, HIV-1 recombinant Nef protein is able to decrease phagocytosis of apoptotic PMNL from normal human macrophages in a dose-dependent manner. The results of our study suggest that impaired macrophage phagocytosis of PMNL apoptotic bodies may contribute to the persistence of the inflammatory state in HIV-infected subjects, especially during opportunistic infections that are often favored by defective phagocytic activity.     

Effect of Antiretroviral Therapy on Cryptosporidiosis and Microsporidiosis in Patients Infected with Human Immunodeficiency Virus Type 1

 To better understand whether potent antiretroviral therapies can modify the natural history of HIV-1-associated microsporidiosis and cryptosporidiosis, the response to antimicrobial treatment of these opportunistic infections was evaluated in patients with or without antiretroviral treatment. Fifty patients with diarrhoea, all positive for Cryptosporidium parvum or Enterocytozoon bieneusi, were included in the study. Retrospective data were collected concerning demographics, clinical and microbiological characteristics of the parasitic infection, antiretroviral therapy and prophylaxis against opportunistic infections. Faecal samples were prepared using the Richie formalin-ethyl acetate method and stained using the modified Ziehl-Neelsen method for detection of Cryptosporidium parvum and Isospora belli, the modified trichrome and calcofluor white technique for detection of Enterocytozoon spp., and iodine for detection of ova, cysts or vegetative forms. Diarrhoea was defined as an abnormal increase in stool liquidity, an abnormal increase in stool frequency and a daily stool weight of more than 250 g for a period of at least 4 days. Patients treated with double antiretroviral therapy or protease inhibitors demonstrated an excellent response and a sustained therapeutic effect after follow-up (range, 5–36 months). The relapse of cryptosporidiosis in two patients who discontinued antiretroviral therapy suggests that the infection might remain in a latent stage. The resolution of the diarrhoea seems to be related to an increased CD4+ cell count rather than to the viral load. In conclusion, these data strongly support the hypothesis that combination antiretroviral therapy is able to greatly modify the course of cryptosporidiosis and microsporidiosis in patients infected with HIV-1.     

Phagocytic Function of Monocytes in Children with Human Immunodeficiency Virus Type 1 Infection

We investigated the phagocytic function of monocytes in 7- to 10-year-old children horizontally infected with human immunodeficiency virus type 1 (HIV-1) in comparison to that in healthy sex- and age-matched controls. CR3-mediated phagocytosis was increased in patients with HIV-associated pulmonary tuberculosis, independently of CD4 counts and p24 antigenemia.     

Hepatitis in Mice Infected with Coxsackie Virus B1

The livers of mice of different ages were readily damaged by Coxsackie virus B₁ infection. The severity of liver damage decreased as the age of the mice increased. Coxsackie B₁ viral crystals were not found in the damaged liver cells in spite of severe pathological changes of the liver, both histologically and electron microscopically, and even though characteristic crystal formation was observed in the pancreas of three of these same animals. Nevertheless, the hepatic damage was considered to be due to direct viral invasion of the hepatic cells. This injury was followed by a variety of degenerative and necrotic processes displaying somewhat characteristic morphological manifestations. The severe hepatic infection produced in the newborn mice resulted in their death from a rather fulminating illness, whereas in the older mice there was recovery from mild to moderate hepatic injury with cellular regeneration by the fourth day after viral inoculation. The experimental preparation used here provides an excellent means for the study of the processes of injury and healing of the liver infected with a virus that is also infectious for man.     

False-Positive Tests for Syphilis Associated with Human Immunodeficiency Virus and Hepatitis B Virus Infection among Intravenous Drug Abusers

 The role of HIV, hepatitis C virus, and hepatitis B virus infections in the production of biological false-positive reactions for syphilis was evaluated in two large samples of intravenous drug abusers and homosexual men attending AIDS prevention centers in Spain. A significantly increased odds ratio (OR) for false-positive tests for syphilis [OR 2.23, 95% confidence intervals (CI) 1.76–2.83] was observed for HIV-seropositive intravenous drug abusers; biological false-positive reactions were also more frequent (OR 1.73, 95% CI 1.30–2.31) among intravenous drug abusers who were hepatitis B virus seropositive but not among those who were hepatitis C virus seropositive (OR 0.90; 95% CI 0.48–1.69). Among homosexuals, the association between HIV and biological false-positive reactions was restricted to subjects who were also intravenous drug abusers, indicating the crucial role of intravenous drug abuse. Only 20.5% of intravenous drug abusers with a previous biological false-positive reaction yielded a false-positive result in their subsequent visit.     

Clinical Features of Seizures in Patients with Human Immunodeficiency Virus Infection

Patients with human immunodeficiency virus (HIV) infection have a higher burden of seizures, but few studies have examined seizures in HIV-infected individuals in Korea. A retrospective study was conducted to determine the epidemiology and clinical characteristics of seizures in patients with HIV infection. Among a total of 1,141 patients, 34 (3%) had seizures or epilepsy; 4 of these individuals had epilepsy before HIV infection, and the others showed new-onset seizures. Most patients exhibited moderate (200 to 500, n = 13) or low (below 200, n = 16) CD4 counts. The most common seizure etiology was progressive multifocal leukoencephalopathy (n = 14), followed by other HIV-associated central nervous system (CNS) complications (n = 6). Imaging studies revealed brain lesions in 21 patients. A total of 9 patients experienced only one seizure during the follow-up period, and 25 patients experienced multiple seizures or status epilepticus (n = 2). Multiple seizures were more common in patients with brain etiologies (P = 0.019) or epileptiform discharges on EEG (P = 0.032). Most seizures were controlled without anticonvulsants (n = 12) or with a single anticonvulsant (n = 12). Among patients with HIV infection, seizures are significantly more prevalent than in the general population. Most seizures, with the exception of status epilepticus, have a benign clinical course and few complications.

Graphical Abstract

相似文献   

Natural History of Intestinal Microsporidiosis among Patients Infected with Human Immunodeficiency Virus

A chart review of 73 human immunodeficiency virus (HIV)-infected patients with enteric microsporidiosis was conducted to define the natural history of microsporidiosis. A substantial proportion of patients remained symptomatic after 6 months (54.8% with persistent diarrhea and 51.2% with weight loss). Predictors for persistent diarrhea included high HIV RNA viral load and no initiation of protease inhibitor therapy.     

Response to Standard Syphilis Treatment in Patients Infected with the Human Immunodeficiency Virus

 In a study designed to evaluate the efficacy of penicillin in HIV-infected patients with syphilis and to determine the clinical and laboratory responses after treatment, 13 patients with HIV infection and syphilis were assessed at enrollment and at the last follow-up examination (median time of 21 months). The Venereal Diseases Research Laboratory (VDRL) test, the Treponema pallidum hemaglutination test, and leukocyte counts in cerebrospinal fluid were evaluated both at enrollment and at the last follow-up visit, and the polymerase chain reaction for Treponema pallidum DNA and the rabbit infectivity test were performed on cerebrospinal fluid samples at the last follow-up visit. Primary syphilis was confirmed in four patients, latent syphilis in five, and neurosyphilis in four. After penicillin treatment, all patients were asymptomatic. The serum rapid plasma reagin test became negative in five patients, and titers declined in eight. The VDRL test, Treponema pallidum DNA, and the rabbit infectivity test were negative in all 13 patients. Except for one patient whose serological titer was slow to decline, all patients had good clinical and serological responses to penicillin. In certain settings, factors other than penicillin treatment failure should be considered in HIV-infected patients with suspected relapse of syphilis.     

Diagnosis of Human Immunodeficiency Virus Type 1 Infection with Different Subtypes Using Rapid Tests

We evaluated six rapid tests for their sensitivity and specificity in diagnosing human immunodeficiency virus type 1 (HIV-1) infection using 241 specimens (172 HIV-1 positive, 69 HIV-1 negative) representing different HIV-1 subtypes (A [n = 40], B [n = 47], C [n = 28], E [n = 42], and F [n = 7]). HIVCHEK, Multispot, RTD and SeroStrip were 100% sensitive and specific. Capillus failed to identify two of eight subtype C specimens (overall sensitivity of 98.85%), while the SUDS test (the only test approved by the Food and Drug Administration) gave false-positive results for 5 of 69 seronegative specimens (specificity of 93.24%). Our results suggest that although rapid tests perform well in general, it may be prudent to evaluate a rapid test for sensitivity and specificity in a local population prior to its widespread use.     

Immunoblot Profile as Predictor of Toxoplasmic Encephalitis in Patients Infected with Human Immunodeficiency Virus

In order to define more accurately human immunodeficiency virus-infected patients at risk of developing toxoplasmic encephalitis (TE), we assessed the prognostic significance of the anti-Toxoplasma gondii immunoglobulin G (IgG) immunoblot profile, in addition to AIDS stage, a CD4⁺ cell count <50/mm³, and an antibody titer ≥150 IU/ml, in patients with CD4 cell counts <200/mm³ and seropositive for T. gondii. Baseline serum samples from 152 patients included in the placebo arm of the ANRS 005-ACTG 154 trial (pyrimethamine versus placebo) were used. The IgG immunoblot profile was determined using a Toxoplasma lysate and read using the Kodak Digital Science 1D image analysis software. Mean follow-up was 15.1 months, and the 1-year incidence of TE was 15.9%. The cumulative probability of TE varied according to the type and number of anti-T. gondii IgG bands and reached 65% at 12 months for patients with IgG bands of 25 and 22 kDa. In a Cox model adjusted for age, gender, Centers for Disease Control and Prevention (CDC) clinical stage, and CD4 and CD8 cell counts, the incidence of TE was higher when the IgG 22-kDa band (hazard ratio [HR] = 5.4; P < 0.001), the IgG 25-kDa band (HR = 4.7; P < 0.001), or the IgG 69-kDa band (HR = 3.4; P < 0.001) was present and was higher for patients at CDC stage C (HR = 4.9; P < 0.001). T. gondii antibody titer and CD4 cell count were not predictive of TE. Thus, detection of IgG bands of 25, 22, and/or 69 kDa may be helpful for deciding when primary prophylaxis for TE should be started or discontinued, especially in the era of highly active antiretroviral therapy.     

Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection

In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8⁺ and CD4⁺ T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4⁺ T cells with the virus; (iii) inactivation of the virus in CD4⁺ T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4⁺ T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4⁺ T cells. CD4⁺ T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID₅₀; which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4⁺ T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID₅₀ of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 μg/ml) and UVB irradiation (312 nm) reduced the TCID₅₀ of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4⁺ T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137).Antiretroviral therapy (ART) has been widely used to suppress human immunodeficiency virus type 1 (HIV-1) replication and increase the number of CD4⁺ T cells in patients with HIV-1 infection. However, in most of these patients, the recovery of anti-HIV-1-specific T-cell function is incomplete. As the complete restoration of T-cell immune function is considered to be necessary for effective control of the viral infection, additional measures aimed at the bolstering of the HIV-1-specific adaptive immunity in patients treated with ART are being evaluated.Dendritic cells (DCs) are the most potent antigen-presenting cells that can both prime and sustain memory responses (24, 28). DCs have been used increasingly frequently in vaccines against cancer and viral infections (4, 13, 20). Previous studies from our group showed that DCs derived from the blood of subjects with chronic progressive HIV-1 infection and not receiving ART were able to stimulate anti-HIV-1 reactivity (5). HIV-1-reactive CD8⁺ T cells are detectable in the peripheral circulation of subjects receiving ART following in vitro activation with many types of HIV-1 antigens, including HIV-1 proteins, HIV-1 peptides, and virus-infected apoptotic cell-loaded matured DCs (6, 10, 14, 22, 23, 31). We hypothesized that it may be possible to reconstitute the reactivity of naïve and memory virus-specific T cells by delivering to patients autologous DCs engineered ex vivo to express and present known immunodominant peptides of HIV-1. To this end, we have recently completed a phase I clinical protocol in which autologous monocyte-derived DCs were pulsed with a mix of three HIV-1 peptides (Gag, Pol, and Env) and one influenza A virus (matrix) major histocompatibility complex class I supertype peptide and delivered as vaccines to 18 HIV-1-infected, ART-treated subjects (5). This vaccination strategy was found to be safe and feasible and resulted in a transient but significant increase in the frequency of CD8⁺ T cells specific for HIV-1 peptides present in the vaccine (5). On the basis of the results of this trial, we have been considering a strategy of stimulating HIV-1-specific, naïve CD8⁺ and CD4⁺ T cells by priming them with DCs engineered to express autologous HIV-1 (19). The rationale for this strategy is that autologous virus represents a large repertoire of the host''s diverse HIV-1 antigen pool and offers the potential to elicit the most specific, broadest, and most effective immune responses for each subject''s quasispecies of HIV-1, thus increasing vaccine efficacy.In this report, we provide evidence that the production of an antiviral vaccine containing autologous DCs fed with inactivated HIV-1-infected, autologous, apoptotic CD4⁺ T cells is feasible, can be successfully accomplished in a good manufacture practice facility, and can be scaled up for therapeutic delivery to HIV-positive (HIV-1⁺) patients. The production process consists of several steps: (i) isolation of autologous virus from the peripheral blood of HIV-1-infected subjects; (ii) superinfection of autologous enriched CD4⁺ CD8⁻ T cells with viral supernatants; (iii) virus inactivation by psoralen and UVB irradiation; (iv) testing for p24 levels and the residual HIV-1 load by determining the 50% tissue culture infective doses (TCID₅₀) for apoptotic CD4⁺ T cells; and (v) loading of autologous DCs with apoptotic, HIV-1-infected CD4⁺ T cells. Although this process is complex, it has been successfully scaled up for therapeutic vaccine production.     

Hepatitis B Virus (HBV) Mutations Associated with Resistance to Lamivudine in Patients Coinfected with HBV and Human Immunodeficiency Virus

Mutations associated with hepatitis B virus (HBV) resistance to lamivudine have not been extensively addressed in human immunodeficiency virus (HIV)-HBV coinfection. We have studied the HBV polymerase sequences from nine coinfected patients who experienced HBV recurrence while under lamivudine treatment. In seven of these nine patients, Met(550), belonging to the highly conserved YMDD motif, was mutated to Val and was associated with a substitution of Met for Leu(526) in each case. In the two remaining patients, we found a Met(550)-to-Ile change that was associated in only one case with a Leu(526)-to-Met mutation. No mutation was observed in three control patients not receiving lamivudine. This study demonstrates the emergence of particular genetic profiles in HBV-HIV-coinfected patients experiencing a loss of control of HBV infection despite high doses of lamivudine.     

Expression of Regeneration and Tolerance Factor Correlates Directly with Human Immunodeficiency Virus Infection and Inversely with Hepatitis C Virus Infection

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause two of the most prevalent debilitating viral infections. HIV appears to induce a skewing toward a Th2 response, while in HCV infection a Th1 response appears to dominate. Regeneration and tolerance factor (RTF) may participate in driving or sustaining a Th2 cytokine response. The expression of RTF on CD3⁺ T cells of HIV-seropositive (HIV⁺) individuals is increased. The purpose of this study was to compare the expression of RTF during HIV infections with that during HCV infections. Three-color flow-cytometric analysis of peripheral blood collected from HIV⁺ HCV-seropositive (HCV⁺), HIV- and HCV-seropositive (HIV⁺ HCV⁺), and HIV- and HCV-seronegative (HIV⁻ HCV⁻) individuals was performed. Levels of RTF expression on T-lymphocyte subsets from these groups were compared, as were levels of RTF expression on activated T cells expressing CD38 and HLA-DR, to determine the relationship of RTF expression to these infections. We demonstrated that the expression of RTF on surfaces of T cells from HIV⁺ individuals is upregulated and that its expression on T cells from HCV⁺ individuals is downregulated. A twofold increase in the mean channel fluorescence of RTF on CD3⁺ T cells was seen in both HIV⁺ and HIV⁺ HCV⁺ individuals compared to HIV⁻ HCV⁻ individuals. HCV⁺ individuals had lower levels of RTF expression than HIV⁻ HCV⁻ individuals (P < 0.005 for CD4⁺; P < 0.0005 for CD8⁺). In terms of percentages of T cells expressing RTF, the groups were ranked as follows: HIV⁺ > HIV⁺ HCV⁺ > HIV⁻ HCV⁻ > HCV⁺. The results indicate that RTF expression correlates with HIV-associated immune activation and may be associated with Th2-type responses.